tbuckley/cabot-search huggingface dataset:
Household Air Pollution and Child Lung Function: The Ghana Randomized Air Pollution and Health Study
Authors: Prince Darko Agyapong, Darby Jack, Seyram Kaali, Elena Colicino, Mohammed Nuhu Mujtaba, Steven N. Chillrud, Musah Osei, Chris Gennings, Oscar Agyei, Patrick L. Kinney, Adolphine Kwarteng, Matthew Perzanowski, Rebecca Kyerewaa Dwommoh Prah, Theresa Tawiah, Kwaku Poku Asante, Alison G. Lee
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: The impact of a household air pollution (HAP) stove intervention on child lung function is poorly described. Objectives: To assess the effect of a prenatal to age one HAP stove intervention on, and exposure-response associations with, age four lung function. Methods: The Ghana Randomized Air Pollution and Health Study (GRAPHS) randomized pregnant women to a liquefied petroleum gas (LPG), improved biomass, or open fire (control) stove through child age one. We quantified HAP exposure by repeated maternal and child personal carbon monoxide (CO) exposure measurements. Children performed oscillometry, an effort-independent lung function measurement, at age four. We examined associations between GRAPHS stove assignment and prenatal and infant CO measurements and oscillometry via generalized linear regression models. We used reverse distributed lag models (rDLMs) to examine time-varying associations between prenatal CO and oscillometry. Measurements and Main Results: The primary oscillometry measure was reactance at 5 Hertz, X5, a measure of elastic and inertial lung properties. Secondary measures included total, large and small airway resistance (R5, R20, R5-20), area of reactance (AX) and resonant frequency (Fres). Of the 683 children who attended the lung function visit, 567 (83%) performed acceptable oscillometry. Two hundred and twenty-one, 106, and 240 children were from the LPG, improved biomass and control arms, respectively. Compared to control, the improved biomass stove was associated with lower reactance at 5 Hertz (X5 z-score, beta=-0.25, 95% CI -0.39, -0.11), higher large airway resistance (R20 z-score, beta=0.34, 95% CI 0.23, 0.44) and higher area of reactance (AX z-score, beta=0.16, 95% CI 0.06, 0.26) suggestive of overall worse lung function. The LPG stove was associated with higher X5 (beta=0.16, 95% CI 0.01, 0.31) and lower small airway resistance (R5-20 z-score, beta=-0.15, 95% CI -0.30, 0.0) suggestive of better small airway function. Higher average prenatal CO exposure was associated with higher R5 and R20 and DLMs identified sensitive windows of exposure between CO and X5, R5, R20 and R5-20. Conclusions: These data support the importance of prenatal HAP exposure on child lung function. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT01335490.
Long-term vaccination strategies to mitigate the impact of SARS-CoV-2 transmission: A modelling study
Authors: Alexandra B. Hogan, Sean L. Wu, Jaspreet Toor, Daniela Olivera Mesa, Patrick Doohan, Oliver J. Watson, Peter Winskill, Giovanni Charles, Gregory Barnsley, Eleanor M. Riley, David S. Khoury, Neil M. Ferguson, Azra C. Ghani
Journal: PLoS Medicine (2023)

Background Vaccines have reduced severe disease and death from Coronavirus Disease 2019 (COVID-19). However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity. Methods and findings We developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both ancestral and variant-adapted vaccine products, while considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is an efficient strategy, although large numbers of hospitalisations and deaths could be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups was more effective than continuing primary vaccination into younger ages in our model. Our study is limited by uncertainty in key parameters, including the long-term durability of vaccine and infection-induced immunity as well as uncertainty in the future evolution of the virus. Conclusions Our modelling suggests that regular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. Our results suggest that focusing vaccination in the highest-risk cohorts will be the most efficient (and hence cost-effective) strategy to reduce morbidity and mortality.
Association Between T2-related Comorbidities and Effectiveness of Biologics in Severe Asthma
Authors: Michael E. Wechsler, Ghislaine Scelo, Désirée E. S. Larenas-Linnemann, Carlos A. Torres-Duque, Jorge Maspero, Trung N. Tran, Ruth B. Murray, Neil Martin, Andrew N. Menzies-Gow, Mark Hew, Matthew J. Peters, Peter G. Gibson, George C. Christoff, Todor A. Popov, Andréanne Côté, Celine Bergeron, Delbert Dorscheid, J. Mark FitzGerald, Kenneth R. Chapman, Louis Philippe Boulet, Mohit Bhutani, Mohsen Sadatsafavi, Libardo Jiménez-Maldonado, Mauricio Duran-Silva, Bellanid Rodriguez, Carlos Andres Celis-Preciado, Diana Jimena Cano-Rosales, Ivan Solarte, Maria Jose Fernandez-Sanchez, Patricia Parada-Tovar, Anna von Bülow, Anne Sofie Bjerrum, Charlotte S. Ulrik, Karin Dahl Assing, Linda Makowska Rasmussen, Susanne Hansen, Alan Altraja, Arnaud Bourdin, Camille Taille, Jeremy Charriot, Nicolas Roche, Andriana I. Papaioannou, Konstantinos Kostikas, Nikolaos G. Papadopoulos, Sundeep Salvi, Deirdre Long, Patrick D. Mitchell, Richard Costello, Concetta Sirena, Cristina Cardini, Enrico Heffler, Francesca Puggioni, Giorgio Walter Canonica, Giuseppe Guida, Takashi Iwanaga, Mona Al-Ahmad, Ulises García, Piotr Kuna, João A. Fonseca, Riyad Al-Lehebi, Mariko S. Koh, Chin Kook Rhee, Borja G. Cosio, Luis Perez de Llano, Diahn-Warng (Steve) Perng, Erick Wan-Chun Huang, Hao-Chien Wang, Ming-Ju Tsai, Bassam Mahboub, Laila Ibraheem Jaber Salameh, David J. Jackson, John Busby, Liam G. Heaney, Paul E. Pfeffer, Amanda Grippen Goddard, Eileen Wang, Flavia C. L. Hoyte, Nicholas M. Chapman, Rohit Katial, Victoria Carter, Lakmini Bulathsinhala, Neva Eleangovan, Con Ariti, Juntao Lyu, Celeste Porsbjerg, David B. Price
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents.
What do Hyperhidrosis Quality of Life Index (HidroQoL©) scores mean? Transferring science into practice by establishing a score banding system
Authors: Theresa Donhauser, Michaela Gabes, Ebru Özkan, Clarissa Masur, Paul Kamudoni, Sam Salek, Christoph Abels, Christian Apfelbacher
Journal: British Journal of Dermatology (2023)

Abstract Background The Hyperhidrosis Quality of Life Index (HidroQoL©) is a measure of quality of life (QoL) impacts in hyperhidrosis (HH). Objectives We aimed to establish score banding systems for the HidroQoL total score for specific contexts representing different severity/impact categories by using the Dermatology Life Quality Index (DLQI) and the Hyperhidrosis Disease Severity Scale (HDSS) as anchors, including data from 357 patients from a phase III clinical trial. Methods We used the HDSS, the established DLQI score bands and two single items (items 5 and 7) of the DLQI as anchors for the creation of banding systems for the HidroQoL. These anchors were chosen via consensus among an expert group according to relevance to patient experience. Due to the distribution of the HDSS and the single DLQI item 7, receiver operating characteristic curves were computed in order to create an optimal cut-off value of the HidroQoL total score. For the DLQI banding system and the single DLQI item 5, we created a banding system for the HidroQoL based on the distribution of their different categories. Results A score of 30 and greater is proposed as the cut-off value for sweating that ‘always interferes in daily activities’, based on the HDSS as anchor. In terms of overall skin QoL effects, score bands of 0–6, 7–18, 19–25, 26–32 and 33–36 represent ‘no effect’, ‘small effect’, ‘moderate effect’, ‘very large effect’ and ‘extremely large effect’ on the patient’s life, respectively. Conclusions In this study, we propose different banding systems for four different contexts: skin-specific QoL (DLQI banding), HH severity (HDSS), working and studying (single DLQI item 7) and social and leisure activities (single DLQI item 5). These banding systems and cut-off values can be used in clinical research and practice to place the patients in different severity categories.
Proximal and Distal Bronchioles Contribute to the Pathogenesis of Non–Cystic Fibrosis Bronchiectasis
Authors: Takanori Asakura, Kenichi Okuda, Gang Chen, Hong Dang, Takafumi Kato, Yu Mikami, Stephen A. Schworer, Rodney C. Gilmore, Giorgia Radicioni, Padraig Hawkins, Selene Margarita Barbosa Cardenas, Minako Saito, Anne Marie Cawley, Gabriela De la Cruz, Michael Chua, Neil E. Alexis, Yohei Masugi, Peadar G. Noone, Carla M. P. Ribeiro, Mehmet Kesimer, Kenneth N. Olivier, Naoki Hasegawa, Scott H. Randell, Wanda K. O’Neal, Richard C. Boucher
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Non–cystic fibrosis bronchiectasis (NCFB) may originate in bronchiolar regions of the lung. Accordingly, there is a need to characterize the morphology and molecular characteristics of NCFB bronchioles. Objectives: Test the hypothesis that NCFB exhibits a major component of bronchiolar disease manifest by mucus plugging and ectasia. Methods: Morphologic criteria and region-specific epithelial gene expression, measured histologically and by RNA in situ hybridization and immunohistochemistry, identified proximal and distal bronchioles in excised NCFB lungs. RNA in situ hybridization and immunohistochemistry assessed bronchiolar mucus accumulation and mucin gene expression. CRISPR-Cas9–mediated IL-1R1 knockout in human bronchial epithelial cultures tested IL-1α and IL-1β contributions to mucin production. Spatial transcriptional profiling characterized NCFB distal bronchiolar gene expression. Measurements and Main Results: Bronchiolar perimeters and lumen areas per section area were increased in proximal, but not distal, bronchioles in NCFB versus control lungs, suggesting proximal bronchiolectasis. In NCFB, mucus plugging was observed in ectatic proximal bronchioles and associated nonectatic distal bronchioles in sections with disease. MUC5AC and MUC5B mucins were upregulated in NCFB proximal bronchioles, whereas MUC5B was selectively upregulated in distal bronchioles. Bronchiolar mucus plugs were populated by IL-1β–expressing macrophages. NCFB sterile sputum supernatants induced human bronchial epithelial MUC5B and MUC5AC expression that was >80% blocked by IL-1R1 ablation. Spatial transcriptional profiling identified upregulation of genes associated with secretory cells, hypoxia, interleukin pathways, and IL-1β–producing macrophages in mucus plugs and downregulation of epithelial ciliogenesis genes. Conclusions: NCFB exhibits distinctive proximal and distal bronchiolar disease. Both bronchiolar regions exhibit bronchiolar secretory cell features and mucus plugging but differ in mucin gene regulation and ectasia.
Pseudouridine synthase 1 promotes hepatocellular carcinoma through mRNA pseudouridylation to enhance the translation of oncogenic mRNAs
Authors: Yan-Xia Hu, Li-Ting Diao, Ya-Rui Hou, Guo Lv, Shuang Tao, Wan-Yi Xu, Shu-Juan Xie, Ya-Han Ren, Zhen-Dong Xiao
Journal: Hepatology (2023)

Background and Aims: Pseudouridine is a prevalent RNA modification and is highly present in the serum and urine of patients with HCC. However, the role of pseudouridylation and its modifiers in HCC remains unknown. We investigated the function and underlying mechanism of pseudouridine synthase 1 (PUS1) in HCC. Approach and Results: By analyzing the TCGA data set, PUS1 was found to be significantly upregulated in human HCC specimens and positively correlated with tumor grade and poor prognosis of HCC. Knockdown of PUS1 inhibited cell proliferation and the growth of tumors in a subcutaneous xenograft mouse model. Accordingly, increased cell proliferation and tumor growth were observed in PUS1-overexpressing cells. Furthermore, overexpression of PUS1 significantly accelerates tumor formation in a mouse HCC model established by hydrodynamic tail vein injection, while knockout of PUS1 decreases it. Additionally, PUS1 catalytic activity is required for HCC tumorigenesis. Mechanistically, we profiled the mRNA targets of PUS1 by utilizing surveying targets by apolipoprotein B mRNA-editing enzyme 1 (APOBEC1)-mediated profiling and found that PUS1 incorporated pseudouridine into mRNAs of a set of oncogenes, thereby endowing them with greater translation capacity. Conclusions: Our study highlights the critical role of PUS1 and pseudouridylation in HCC development, and provides new insight that PUS1 enhances the protein levels of a set of oncogenes, including insulin receptor substrate 1 (IRS1) and c-MYC, by means of pseudouridylation-mediated mRNA translation.
Base editing of the mutated TERT promoter inhibits liver tumor growth
Authors: Gaoxiang Zhao, Qingxia Ma, Huang Yang, Hongfei Jiang, Qianqian Xu, Shudi Luo, Zhaoyuan Meng, Juanjuan Liu, Lei Zhu, Qian Lin, Min Li, Jing Fang, Leina Ma, Wensheng Qiu, Zhengwei Mao, Zhimin Lu
Journal: Hepatology (2023)

Background and Aims: Base editing has shown great potential for treating human diseases with mutated genes. However, its potential for treating HCC has not yet been explored. Approach and Results: We employed adenine base editors (ABEs) to correct a telomerase reverse transcriptase ( TERT ) promoter mutation, which frequently occurs in various human cancers, including HCC. The mutated TERT promoter −124 C&gt;T is corrected to −124 C by a single guide (sg) RNA-guided and deactivated Campylobacter jejuni Cas9 (CjCas9)-fused adenine base editor (CjABE). This edit impairs the binding of the E-twenty six/ternary complex factor transcription factor family, including E-twenty six-1 and GABPA, to the TERT promoter, leading to suppressed TERT promoter and telomerase activity, decreased TERT expression and cell proliferation, and increased cell senescence. Importantly, injection of adeno-associated viruses expressing sgRNA-guided CjABE or employment of lipid nanoparticle-mediated delivery of CjABE mRNA and sgRNA inhibits the growth of liver tumors harboring TERT promoter mutations. Conclusions: These findings demonstrate that a sgRNA-guided CjABE efficiently converts the mutated TERT promoter −124 C&gt;T to −124 C in HCC cells and underscore the potential to treat HCC by the base editing-mediated correction of TERT promoter mutations.
Association of accelerometer-measured physical activity intensity, sedentary time, and exercise time with incident Parkinson’s disease
Authors: Mengyi Liu, Xiaoqin Gan, Ziliang Ye, Yuanyuan Zhang, Panpan He, Chun Zhou, Sisi Yang, Yanjun Zhang, Xianhui Qin
Journal: npj Digital Medicine (2023)

Abstract Evidence regarding the association between physical activity and Parkinson’s disease (PD) risk is generally limited due to the use of self-report questionnaires. We aimed to quantify the separate and combined effects of accelerometer-measured light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), sedentary time and exercise timing with incident PD. 96,422 participants without prior PD and with usable accelerometer data were included from UK Biobank. Time spent in sedentary activity, LPA, MVPA, and exercise timing were estimated using machine learning models. The study outcome was incident PD. Over a median follow-up duration of 6.8 years, 313 participants developed PD. There was a L-shaped association for LPA and MVPA, and a reversed L-shaped association for sedentary time, with the risk of incident PD (all P for nonlinearity &lt; 0.001). Similar trends were found across three time-windows (morning, midday-afternoon, and evening). Compared with those with both low LPA (&lt;3.89 h/day) and low MVPA (&lt;0.27 h/day), the adjusted HR (95% CI) of PD risk was 0.49 (0.36–0.66), 0.19 (0.36–0.66) and 0.13 (0.09–0.18), respectively, for participants with high MVPA only, high LPA only, and both high LPA and high MVPA. Moreover, participants with both low LPA and high sedentary time (≥9.41 h/day) (adjusted HR, 5.59; 95% CI: 4.10–7.61), and those with both low MVPA and high sedentary time (adjusted HR, 3.93; 95% CI: 2.82–5.49) had the highest risk of incident PD. In conclusion, regardless of exercise timing (morning, midday-afternoon, and evening), there was an inverse association for accelerometer-measured MVPA and LPA, and a positive association for sedentary time, with incident PD.
The Role of Dual-Phase 18F-FP-CIT PET to Early Diagnosis of Corticobasal Syndrome
Authors: Min Seung Kim, Dong Gueu Park, In Ja Shin, Young Sil An, Jung Han Yoon
Journal: Clinical Nuclear Medicine (2023)

Background Corticobasal syndrome (CBS) is a neurodegeneration characterized by asymmetric parkinsonism, dystonia, myoclonus, and apraxia. In the early stage, CBS presents with asymmetric parkinsonism and cortical symptoms (apraxia and alien hand), and neuroimaging finding is often vague, making early clinical differentiation from idiopathic Parkinson disease (IPD) challenging. This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter (DAT) uptake using dual-phase FP-CIT PET in discriminating between CBS and IPD at early stage. Patients and Methods The study enrolled clinically diagnosed CBS (n = 11) and IPD (n = 22) patients (age and sex matched). All participants underwent dual-phase 18 F-FP-CIT PET, and regional SUV ratio (SUVR) was obtained by semiquantitative analysis. The early perfusion imaging and DAT imaging were compared between groups. Results The regional SUVRs (early phase) of the frontal lobe, thalamus, cingulate, and caudate were significantly lower in patients with CBS, whereas the SUVR of occipital lobe was lower in the IPD group. The CBS group exhibited more prominent asymmetry than the IPD group, particularly in the perirolandic area, superior frontal gyrus, and anterior parietal lobe in early phase PET. Striatal DAT uptake (delayed phase) revealed that the caudate showed lower SUVR and prominent asymmetry in the CBS group, and the caudate-to-putamen ratio (CP ratio) was significantly lower in CBS patients ( P &lt; 0.001). Among the parameters (early and delayed), the CP ratio in DAT exhibited the most powerful discriminative power from receiver operating characteristic curve comparison (area under curve = 0.983). Conclusions This study demonstrated that the dual-phase FP-CIT PET is useful in differentiating CBS and IPD in the early stage of the disease, and a lower CP ratio of DAT imaging is highly informative for distinguishing between corticobasal degeneration and IPD.
Vasculitis that did not read the books
Authors: Ana C Bardan-Inchaustegui, Jorge A Esquivel-Valerio, Rodrigo de Jesus Castillo-de la Garza, Jesus Alberto Cardenas-de la Garza, Valeria Gonzalez-Gonzalez, Dionicio Angel Galarza-Delgado
Journal: Annals of the Rheumatic Diseases (2023)
A Rare Clinical Presentation With a Difficult Imaging Diagnosis of an Intra-articular Clear Cell Sarcoma of the Knee
Authors: Tomonori Kawasaki, Jiro Ichikawa, Hiroki Imada, Kojiro Onohara, Tomoaki Torigoe
Journal: Clinical Nuclear Medicine (2023)

Clear cell sarcoma, a highly aggressive cell sarcoma with melanotic differentiation, typically occurs in the tendon and aponeuroses of the lower extremities and rarely develops in the intra-articular region. Herein, we present an extremely rare case of clear cell sarcoma originating from the intra-articular knee and suspected as benign tumors due to the benign-looking findings on MRI and PET/CT. The image results in our case were completely consistent with a tenosynovial giant cell tumor, resulting in the misdiagnosis. For differential diagnosis, especially malignant melanoma, histopathology, including IHC and FISH, was indispensable.
Incidental Identification of Osteoid Osteoma of Skull Bone on 68Ga-PSMA PET/CT
Authors: Kumar Gaurav, Gadde Sathya Sunil, Ritu Verma, Ethel Shangne Belho, Nitin Gupta
Journal: Clinical Nuclear Medicine (2023)

Abstract An osteoid osteoma (OO) is a benign bone neoplasm, characterized by significant nocturnal pain that usually responds to nonsteroidal anti-inflammatory drugs. It occurs most commonly in the lower extremities and vertebrae. Here, we present a case of carcinoma prostate, who was referred to our department for 68 Ga-PSMA PET/CT scan, and we incidentally found out PSMA-avid OO involving frontal bone of skull, which is a rare finding. To the best of our knowledge, this is the second case in which high PSMA uptake is found in the OO, suggesting a possible PSMA expression related to osteoblastic activity.
Solitary Dural Metastasis From Neuroblastoma Detected by 123I-MIBG SPECT/CT
Authors: Xia Lu, Yanfeng Xu, Wei Wang, Jigang Yang
Journal: Clinical Nuclear Medicine (2023)

Abstract 123 I-MIBG SPECT/CT was performed for follow-up in an asymptomatic 8-year-old girl with a history of neuroblastoma. The images showed an unsuspected abnormal accumulation in the head, which was identified as a hyperdense lesion of the dura with increasing MIBG uptake, suggesting the possibility of metastasis from neuroblastoma. A brain MRI with contrast showed a remarkably enhanced lesion beside the confluence of sinuses, which mimicked meningioma. Results of the surgical pathology are consistent with the diagnosis of dural metastasis from neuroblastoma.
An optimization framework to guide the choice of thresholds for risk-based cancer screening
Authors: Adam R. Brentnall, Emma C. Atakpa, Harry Hill, Ruggiero Santeramo, Celeste Damiani, Jack Cuzick, Giovanni Montana, Stephen W. Duffy
Journal: npj Digital Medicine (2023)

It is uncommon for risk groups defined by statistical or artificial intelligence (AI) models to be chosen by jointly considering model performance and potential interventions available. We develop a framework to rapidly guide choice of risk groups in this manner, and apply it to guide breast cancer screening intervals using an AI model. Linear programming is used to define risk groups that minimize expected advanced cancer incidence subject to resource constraints. In the application risk stratification performance is estimated from a case-control study (2044 cases, 1:1 matching), and other parameters are taken from screening trials and the screening programme in England. Under the model, re-screening in 1 year for the highest 4% AI model risk, in 3 years for the middle 64%, and in 4 years for 32% of the population at lowest risk, was expected to reduce the number of advanced cancers diagnosed by approximately 18 advanced cancers per 1000 diagnosed with triennial screening, for the same average number of screens in the population as triennial screening for all. Sensitivity analyses found the choice of thresholds was robust to model parameters, but the estimated reduction in advanced cancers was not precise and requires further evaluation. Our framework helps define thresholds with the greatest chance of success for reducing the population health burden of cancer when used in risk-adapted screening, which should be further evaluated such as in health-economic modelling based on computer simulation models, and real-world evaluations.